CATIONIC AMPHIPHILE-MEDIATED TRANSFER OF THE ENZYME/PRODRUG GENE INTO C_6 GLIOMA CELLS-AN EFFECTIVE IN VITRO CHEMOSENSITIVITY SYSTEM

Objectivs Enzyme/prodrug gene therapy provides a potential strategy for the treatment of glioma.Because of the limitations of using viral vectors for clinical application, we investigated the feasibility of cationicamphiphile-mediated enzyme/prodrug gene transfer into C6 glioma cells. Methods Rat C6 glioma cells weretransfected with pUT599plasmid encoding the herpes simplex virus thymidine kinase (HSV-tk) gene via DOTAPand tested for chemosensitivity of prodrug ganciclovir (GCV). To demonstrate in vitro bystander effect, HSV-tkpositive cells were co-cultured with HSV-tk negative cells at varying proportions. Results DOTAP mediatedHSV-tk gene transfer into C6 cells showed 30%-40% of transfection efficiency. HSV-tk infected C6 glioma cellswere rendered sensitive to concentrations of GCV that were 3-4 logs lower than uninfected cells, with an IC05 of0.087μmol/L. In terms of the bystander effect, the viability of co-cultured cells decreased with increasingpopulations of HSV-tk positive cells after GCV treatment. Conclusion C6 cells were successfully transfected withthe HSV-tk gene via cationic amphiphile and displayed a strong bystander effect after GCV treatment. Cationicamphiphile - mediated HSV- tk/GCV chemosensitivity System may have promise as an intratumoral treatment forglioma.